Sheik Hassan Nasrallah's remarks, given in a televised address, were his first public comments since the long-awaited indictment was announced Thursday.
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Nasrallah said the suspects named in the indictment are brothers "who have an honorable history in resisting Israeli occupation." He went on to cast doubt on the UN-backed tribunal investigating the crime and said it was biased.
Nasrallah cited as proof of Israel's plot that Foreign Minister Avigdor Lieberman said the state had cooperated fully with the tribunal investigating Hariri's murder.
He added that the computers use by the tribunal in Beirut had been transferred through a northern crossing with Israel. "What were they doing in Israel? Everyone knows Israel is one of the most technologically developed countries in the world," he wondered.
The arrests, Nasrallah said, are "another step in the long journey whose path is becoming clearer after Israel's defeat and the triumph of the resistance in the last war".
He added that no one had investigated his claims from a previous speech, namely that Israel was responsible for the Hariri assassination. "If they had checked, they would have found enough proof to charge Israel, but they didn't," he said.
"They didn't ask the Israelis anything: Why did you fly drones above Beirut? Why were your agents there? The tribunal was established through clear political motives."
The suggestion that Hezbollah was involved in the 2005 Beirut truck bombing that killed Rafik Hariri threatens to plunge the Arab nation into a new and violent crisis. Hezbollah has denied any role in the killing and vowed never to turn over any of its members.
The bombing that killed Hariri and 22 other people on Feb. 14, 2005, was one of the most dramatic political assassinations in the Middle East. A billionaire businessman, Hariri was Lebanon's most prominent politician after the 15-year civil war ended in 1990.
One of the men named in the indictment, Mustafa Badreddine, has a storied history of militancy.
He is suspected of building the powerful bomb that blew up the US Marine barracks in Beirut in 1983, killing 241 Americans, mostly Marines, according to a federal law enforcement official and a book "Jawbreaker," by Gary Berntsen, a former official who ran the Hezbollah task force at the CIA.
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