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Trimethyltin (TMT) chloride induces limbic system neuro-degeneration, resulting in behavioral alterations including cognitive deficits. The aim of the present study was to investigate the effect of glucogalactan polysaccharide (GA) which purified from the roots of mushroom Agaricus bisporus extract on the Trimethyltin Chloride (TMT) induced neuropathy in rats. Adult male rats (200 ±10 g) were divided into four groups that were fed with basal diet throughout the experiment (28 days). The first group (G I) was control group, the second group (GII) was treated with 300 mg/kg BW GA intraperitoneally (i.p.) daily for 28 day. The third group (GIII) was administered i.p. with 8.0 mg TMT /kg body weight (BW), and the fourth (G IV) was treated like the third group and was injected with GA 300 mg/kg BW daily for 28 day after 48 h of TMT. Many bioactive compounds, which were found in GA did not cause any changes in the second group compared to normal control group. The results revealed that administrated of GA, when given 48 h after TMT treatment exhibited an excellent neuropathy effect, lowering the average of MDA, HSP70, homocystein and the neurotransmitters in brain tissue homogenate and they were markedly reduced by administration of GA to near-normal levels. Neurotransmitters and NO were significantly increased after GA treatment as compared to TMT group. From the comet assay for DNA revealed that, TMT induced statistically significant (P<0.05) increase in the mean value of the tail length and moment. They significantly decreased after GA treatment, suggesting alleviated oxidative stress mediated by TMT. In GA administered TMT-treated rats, they showed improved brain histology and diminished the level of MDA and nitric oxide (NO) in brain tissue and enhanced total antioxidant capacity in serum compared to TMT group. It could be concluded that GA plays effectively positive role in the improvement of brain function after TMT-induced neuropathy. Taken together, our results suggested that the GA should be useful for developing strategies for protecting nervous system and improving the brain.