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Objective: The substantia nigra pars reticular (SNR) is the vital nuclei sending out information from basal ganglia and it plays an important part in motor behavior maintenance and motor regulation. It aims to observe the changes of mGluR4，GABA-ARα1 and GABA-BR1 in substantia nigra pars reticular of rats induced by one single bout of exhaustive exercise, and to discuss the relationship among the expression of mGluR4，GABA-ARα1, GABA-BR1 and exercise fatigue. Methods: Thirty-six male wistar rats were divided into three groups at random including CG, 0EG and 90EG,which having 12 rats. Meanwhile, peripheral blood samples were drawn from the vein of tail at different time points (pre- exercise, exercise for 30 min, exercise for 90 min and exhaustion immediately during exercise, and 30 min and 90 min post exercise) ，and blood concentrations of lactic acid (LD) ，blood urea nitrogen (BUN) and activities of creatine kinase (CK) were detected by automatic analyser. Furthermore, the technique of Immunohistochemistry has been used to indicate the protein expression of metabotropic glutamate receptors like mGluR4 and gamma-aminobutyric acid a receptor like GABAAR1, also gamma-aminobutyric acid B receptor like GABAB1. Results: The expression level of mGluR4 in SNR in immediately post-exercise group (0EG) and 90 min post-exercise group (90EG) increase significantly than control group (CG), and the expression level of GABA-ARα1 in SNR at 0EG and 90EG were also significantly higher than control group, and GABA-BR1 in SNR in 0EG and 90EG were both significantly lower than CG. Moreover, it presented significant increases in the levels of LD, BUN and CK in peripheral blood compared with those at rest. Conclusion: Exercise fatigue could result in up-regulation of mGluR4 expression，GABA-ARα1 and down-regulation of GABA-BR1 expression in substantia nigra pars reticular of rats, and it also induce the muscle injury by increase the level of LD, CK and BUN in peripheral blood, which suggested that substantia nigra pars reticular was an important brain rigion to modulate the motor function, and mGluR4，GABA-ARα1 and GABA-BR1 were three important receptors related with the muscle injury induced by exercise fatigue. So the mGluR4, GABA-ARα1 and GABA-BR1 could be the new novel substance produced to prevent from exercise fatigue.