Objective To analyze the effects of memantine hydrochloride on the Alzheimer disease （AD） patients， the serum S100B protein and the anti-brain anti-body（ABAb） levels， and to discuss the possible effect of S100B and ABAb on the progression of AD. Methods In this study， 32 AD patients（ AD group） and 40 volunteers without cognitive impairment（ control group） were enrolled. AD patients received treatment of memantine hydrochloride（ dose： 10-20mg/d） for 6 months， and were interviewed at the baseline，the 3rd and the 6th month from the beginning of the treatment. The cognitive function and living ability were assessed with Mini- Mental State Examination（ MMSE） and Activity of Daily Living scale（ ADL）. The cognitive function of patients was further evaluated with Alzheimer Disease Assessment Scale Cognitive Sub-scale（ ADAS-Cog）. The serum S100B and ABAb levels were examined by enzyme linked immunosorbent assay（ ELISA）. Results The S100B and ABAb levels of AD patients were markedly increased compared with the control group（ P＜0.01）. Analysis of variance of repeated measures indicated that there were significant differences in the serum S100B［ （0.66±0.17）， （0.58±0.18），（ 0.50±0.14）μg/L；F=35.22，P＜0.01］ and ABAb levels［ （1.93±0.95），（ 1.65±0.81），（ 1.30± 0.70）U/L；F=42.93，P＜ 0.01］among the baseline and the visit points of 3rd and 6th month after the beginning of the treatment， however， there was no significant difference in the scores of the MMSE， ADL and ADAS-Cog. Conclusions Memantine hydrochloride might effect on the progression of patients with moderate and severe AD by decreasing the S100B protein and ABAb levels.