The academics' warning comes as Japan moves closer to joining the U.S.-led free trade negotiations, currently involving 11 nations.
The professors, in a petition to Japanese Prime Minister Shinzo Abe and Farm Minister Yoshimasa Hayashi, warned Japan may not be able to protest its national interests once its joins the talks, Kyodo News reported.
University of Tokyo Professor Emeritus Satoshi Daigo and Keio University's Masaru Kaneko said the TPP may harm Japan's farming as well as its medical system and food safety standards.
The warning came as Mexican President Enrique Pena Nieto ended his four-day Japan visit Wednesday.
Mexico, one of the countries involved in the TPP negotiations, has supported Japan's participation. The United States is expected to complete its talks this weekend on Japan's participation. Japan also needs to win the support of Australia, Canada and New Zealand.
The government of Abe last month announced its decision to join the TPP talks, although there remain concerns the free-trade deal's tariff elimination provisions could harm Japan's protected agriculture sector through cheap imports. Kaneko warned there is no guarantee Japan can win sanctuaries or exceptions to the TPP's tariff elimination through bilateral dialogue.
"We won't know until the very end how (many sanctuaries) we can secure," Kaneko told reporters.
Kyodo reported Japan has agreed to allow the United States to retain its tariffs on Japanese car and truck imports, effectively in exchange for the tariffs Japan imposes on sensitive agricultural produce.
At his news conference in Tokyo, the Mexican president was guarded in his response to Japan's efforts to retain tariffs on rice and some other farm products, Kyodo said.
"For items each country wants to withhold (from tariff elimination) and differences between countries, separate negotiating tables have been set up, and they should therefore be dealt with there," Pena Nieto was quoted as saying.
He also said he supported Japan's bid to join the TPP talks based on gains from an existing free-trade agreement between Japan and Mexico.
The Wall Street Journal reported with Japan facing strong opposition from its farmers, its participation in the TPP talks may come too late to influence their outcome. Japan's participation also is opposed by its doctor groups, which fear the TPP might harm Japan's universal healthcare service.
"Mexico's endorsement may put pressure on the United States to speed up bilateral preparatory talks with Japan for TPP negotiations," Junichi Sugawara, a trade expert at Mizuho Research Institute, told the Journal.