The purpose of this study was to observe the effects of swainsonine in Oxytropis kansuensis on the expression of Golgi α-mannosidase II (MAN2A1) in the brain tissues of Sprague-Dawley (SD) rats. Twenty-four SD rats were randomly divided into four groups (experimental groups I, II, and III and a control group) of six animals each. The rats were penned as groups and fed feeds containing either 15% (swainsonine content = 0.003%), 30% (swainsonine content = 0.006%), or 45% (swainsonine content = 0.009%) O. kansuensis for experimental groups I-III, respectively, or complete feed for the control group. One hundred and nineteen days after poisoning, all rats showed neurological disorders at different degrees, which were considered to be successful establishment of a chronic poisoning model of O. kansuensis. Rats were sacrificed, and MAN2A1 expression of brain tissues was detected by immunohistochemistry and RT-PCR. The results showed that MAN2A1 was either not expressed or lowly expressed in the molecular layer of the cerebral cortex and hippocampal layers, but was found to be highly expressed in other areas of the brain. MAN2A1 expression decreased in the cerebrum and cerebellum in experimental groups when compared to the control group, whereas the expression of MAN2A1 mRNA was inhibited in cerebral and cerebellar tissues by O. kansuensis. These results indicated that O. kansuensis treatment could reduce the expression of MAN2A1 in brain tissues of SD rats.