Objective To observe the effects of MCI-186 on the cognitive function and DNA oxidative stress in the rat model of cognitive impairment induced by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ).Methods Sixty-four adult male Sprague-Dawley rats were randomly divided into 4 groups: Sham (S), MCI-186+Sham (M+S), ICV-STZ Lesion (L), and MCI-186+Lesion (M+L). The step-down test was used to evaluate potential deficits in memory retention. Spatial learning and memory were tested using the Morris water maze (MWM). The content of hydrogen peroxide (H₂O₂) and activity of catalase (CAT) in the cerebral cortex and hippocampal neurons were determined by colorimetric method. Immunofluorescence staining was used to measure the expression of 8OHdG.Results In the step-down test, compared with the S group, the L group had a significantly reduced latency (179.1±41.3) but a significantly increased number of errors (3.88±0.87) (P<0.05 for both); compared with the L group, the M+L group had a significantly increased latency (250.5±27.1) but a significantly reduced number of errors (2.83±0.64) (P<0.05 for both). The MWM test showed that the L group had a significantly longer latency (36.1±3.59) than the S group (P<0.05), and the M+L group had a significantly shorter latency (18.63±3.73) than the L group (P<0.05). Compared with the L group, the M+L group had a significantly reduced content of H₂O₂ (P<0.05), a significantly increased activity of CAT (P<0.05), and a significantly decreased positive rate of 8OHdG expression (P<0.05).Conclusions MCI-186 can reduce the STZ-induced cognitive impairment and DNA oxidative stress in rats.