However, the BBC's Oana Lungescu in Brussels says the third failed referendum in three years on the EU's reform plans is bound to undermine the bloc's public legitimacy and dent its confidence when it faces other big players on the world stage.
France and Germany quickly issued a joint statement expressing regret over the Irish result.
European leaders earlier said they had no "plan B" for how to proceed if Ireland's electorate voted No.
Declan Ganley of the anti-treaty lobby group Libertas said that if the No vote had indeed triumphed that it was "a great day for Ireland".
"The people of Ireland have shown enormous courage and wisdom in analysing the facts presented to them and making the decision they have," Mr Ganley said.
The No campaign was a broad coalition ranging from Libertas to Sinn Fein, the only party in parliament to oppose the treaty.
Correspondents say many voters did not understand the treaty despite a high-profile campaign led by Mr Cowen, which had the support of most of the country's main parties.
Jose Manuel Barroso said the EC respected the vote but had hoped for another outcome
Mr Cowen accused the No camp of "misrepresentation", saying voters had voiced concern about "issues that clearly weren't in the treaty at all", the Irish Times reported.
Turnout is said to have been about 45%. Commentators had predicted that a low turnout figure would suggest a rejection.
The treaty, which is designed to help the EU cope with its expansion into eastern Europe, provides for a streamlining of the European Commission, the removal of the national veto in more policy areas, a new president of the European Council and a strengthened foreign affairs post.
The treaty is due to come into force on 1 January 2009.
Fourteen countries out of the 27 have completed ratification so far.
The Lisbon Treaty replaces a more ambitious draft constitution that was rejected by French and Dutch voters in 2005.
Just over three million Irish voters are registered - in a European Union of 490 million people.
In 2001, Irish voters almost wrecked EU plans to expand eastwards when they rejected the Nice treaty. It was only passed in a much-criticised second vote.
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