Sulfur dioxide (SO2) and SO2 derivatives colorless are ubiquitous environmental pollutant and an important chemical intermediate in several industrial and food product processes, also are closely related to toxical effect of fluoride in male reproduction.Mitogen-activated protein kinases (MAPKs) is one of the most interconnected pathways, and there are four major branches of the MAPK pathway include the classical MAPK pathway, c-Jun Nterminal kinase (JNK) and p38 MAPK pathway, and the ERK5 pathway, which play an important role in complex cellular programs like proliferation, reproduction, development, transformation, and apoptosis.In order to explore if MAPK signal pathway involve in the reproductive toxicity mechanisms of fluoride and Sodium Sulfite, 72 healthy male Kunming mice were employed for Fluoride (150 mg/L NaF) and Sodium Sulfite (500 mg/L Na2SO3) exposure by drinking water alone or combination (150 mg/L NaF+500 mg/L Na2SO3) for 14 weeks, and the MAPK signal pathway (ERK1/2/5, JNK1/2/3 and p38) and transcriptional factors of JNK downstream (C-Jun, JunD, Elk-1 and ATF-2) expression levels were analyzed by Real-time RT-PCR in mice testis.The results showed that: (1) at 7 weeks after exposure, JNK2 mRNA expression levels decreased by 29.6%, 59.3% (P<0.01) and 56.8% (P<0.01), and ERK2 mRNA expression also significant down-regulated from 3 treated groups compared with the control group, respectively.However, ERK1、 JNK1、 JNK3 and ERK5 mRNA expression had no significant changes; (2) At 14 week, JNK1 expression decreased by 39.1%, 61.8% (P<0.05) and 25.5%, JNK2 expression downed by 48.9%, 39.8% (P<0.01) and 37.5%, respectively, and that ERK5 expression increased significantly in treatment groups.Nevertheless, ERK1, ERK2, JNK3 and p38 mRNA expression levels had no influenced distinctly by Fluoride, Sodium Sulfite or their combination; (3) Fluoride and Sodium Sulfite treatment for 14 weeks up-regulated obviously the transcriptional factors C-Jun and Jun D mRNA expression levels, and unaltered the C-Jun, MAX, Elk-1 and ATF-2 mRNA expression at 7 week after exposure.In conclusion, these results suggested that MAPK signaling pathway play the key role in clarifying mechanisms of male reproductive impairment in animal exposure to F and Sodium Sulfite, especially JNK signaling pathway and regulation transcriptional factors.