Nick Clegg has warned the UK will "turn its back" on the world if it leaves the European Union.
The Deputy Prime Minister, speaking at the Confederation of British Industry (CBI) 2014 conference, said that he wants reform in Brussels but argued that Britain would have "no future at all" if the country left the economic and political union.
"We need to retain and maintain the openness of the British economy. We have always been a great trading nation, we have always been an open society, we have always exported ours goods, our services and our people around the world," said the Liberal Democrat leader.
"In this highly globalised and mobile world economy of ours, there is simply no future at all — for you, for our country — if we turn our backs on the world and pull up the drawbridge. We are nothing if we are not an open and vibrant economy.
"That's where I think, beyond all of the twists and turns of this directive or that directive in Brussels, that's the fundamental importance about this European debate.
"If we can't stand tall in Berlin, Paris and Brussels, how on earth are we going to stand tall in Tokyo, Washington and Beijing. If we turn our backs on our own neighbourhood, we turn our backs on the world."
The comments come after the Prime Minister David Cameron told the CBI conference that his planned 2017 in/out referendum over the UK's membership of the EU would not deter investment into the country.
John Cridland, the director-general of the CBI, said: "The Prime Minister gave an upbeat speech with deficit reduction firmly in pole position.
"There was recognition that it is necessary to grow at the same time as cutting back, and it was good to hear the emphasis on both infrastructure, investment and skills.
"Business will welcome the PM's endorsement of the CBI's Europe strategy of 'In with Reform'."
Ahead of the conference, Business for Britain (BfB) revealed that more than 1,000 UK company leaders now back a renegotiation with the European Union and a referendum.
The campaign group announced that it has signed up more than 1,000 members – just a year and a half after its formation.
The organisation calls for a "better deal" from the EU for the UK and also supports an in/out referendum on the country's membership of the economic and political union.
Clegg also announced new plans to help UK manufacturers to work together with British companies.
The proposal, to be published from the New Year, will encourage and support UK manufacturers to work together with British companies to produce the parts they need, rather than relying on overseas manufacturers.
"Every successful company is only as good as its supply chain. The last four decades have seen the UK's manufacturing base increasingly forced to compete with low-cost economies for investment, jobs and growth," Clegg said.
"Some businesses have struggled and it has resulted in a hollowing out of the UK's domestic supply chains with over half the supplies used in British manufacturing coming from overseas.
"This cannot go on. That's why I'm acting now so we can get off this merry-go-round where every time a manufacturer shifts production overseas, the local companies that support them begin to disappear too.
"These supply industries are huge, important sectors in their own right – our steel makers, petrochemical companies, glass producers all the way down to car seats manufacturers – all of which employ thousands of people and generate millions for our economy but they need our support."