The demonstration Friday in front of Japanese Prime Minister's Yoshihiko Noda's residence came in response to the government's decision to restart two reactors at the Ohi nuclear power plant in Fukui Prefecture, The Asahi Shimbun reported.
Organizers said 150,000 people turned out for the demonstration, while police estimated the crowd at 17,000, The New York Times reported. Local media put the number between 20,000 and 45,000, which the media called the largest protest in central Tokyo since the 1960s.
The two reactors at the Ohi plant, operated by Kansai Electric Power Co., had been shut down for regular maintenance inspections.
In a country where protests are rare, many Japanese residents complain Noda disregarded their safety concerns when he ordered this month the Ohi plant be restarted.
The prime minister said he did so to prevent power shortages that could cause summer blackouts and hurt industry.
The Ohi plant became the first to be restarted since an earthquake and tsunami last March caused the meltdown of the Fukushima nuclear plant.
Weekly rallies against nuclear power began in late March with a few hundred participants.
A 36-year-old Tokyo woman who came to the demonstration with her two young sons Friday said it was the first time she had attended the weekly rally.
"The government never cares about our lives," she said. "I have been a silent observer so far, but I cannot stand aside any longer."
"To restart the nuclear plant without ensuring its safety is crazy," said Naomi Yamazaki, 37, a homemaker. "I know we need these plants for power and jobs, but I don't trust the authorities now to protect us."
Observing the protesters, Noda told reporters as he left his office for his private quarters: "They're making lots of noise."
Similar rallies were held in Nagoya, Nagasaki, Kumamoto and elsewhere.