Assad had yesterday called Paris "a standard-bearer of support for terrorism in Syria since the early days of the conflict", referring to early French support for rebels fighting his regime.
Macron emphasised that France has been focused for years on destroying the Islamic State group as part of a US-led coalition.
"We have been consistent since the beginning" in fighting IS, Macron said at a joint press conference with NATO chief Jens Stoltenberg.
Macron's predecessor Francois Hollande confirmed in 2014 that France had sent weapons to anti-Assad fighters, after providing logistical support to rebels it considered moderate, including Kurds.
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It launched air strikes against IS positions in September 2015, intensifying them two months later after the jihadists claimed responsibility for terrorist attacks in Paris that killed 130 people.
After Macron won the presidency in May, he confirmed that the policy had shifted towards prioritising the destruction of IS rather than ousting Assad, warning of a "failed state" if the leader were forcibly removed.
But he nonetheless said it was crucial to engage him in diplomacy, calling for the regime and opposition forces to join new peace talks next year after the failure of the latest round in Geneva last week.
Paris blamed Damascus for the failure, accusing Assad's government of an "irresponsible strategy of obstruction".
Assad's fate has been the stumbling block to progress in every round of UN-backed indirect negotiations in Geneva so far between his representatives and those of the Syrian opposition.
More than 340,000 people have been killed since the conflict began in March 2011.
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