Objective：To study the effects of anti-depressant-fluoxetine exposure on the CNPase+ oligodendrocytes in CA1 of hippocam－pus in the depressed rats which were induced by chronic unpredictable stress（CUS）. Methods：Male Sprague-Dawley（SD） rats were used，and were randomly divided into control group（n=12） and CUS group（n=３８） after the sucrose preference of the rats was normal and regular. Four weeks CUS and separation was used to build CUS depression model of rats. The sucrose preference was used to screen the depressed rats at the end of 4th week and 12 CUS-induced depressed rats were enrolled as CUS group and 12 as FLX group. The FLX group was treated with fluoxetine at dose of 5 mg/（kg·d） from the fifth week to seventh week. Meanwhile，the control group and the CUS group were treated with saline at the same dose. The CUS group and FLX group were continued exposure to CUS. The total number of CNPase+ oligodendrocytes in the CA1 of hippocampus was investigated with the immunohisto－chemical method and the stereological method. Results：After 7 weeks CUS intervention，the body weight of CUS group（251.4±15.9） g was significantly decreased when compared with that of control group（323.3±25.9） g（P=0.000），but the body weight of CUS group was not significantly different from the body weight of FLX group（257.9±22.7） g（P=0.473）. The sucrose preference of the CUS group（62.0±14.2）% was significantly lower than that of the control group（89.2±4.8）%（P=0.000） and FLX group（78.2±12.8）%（P=0.020）. The stereological results showed that CNPase+ cells in the CA1 field of the hippocampus in CUS group（18 650.7±1 812.0） was significantly decreased compared with that in control group（33 606.9±4 471.4）（P=0.007） and that in FLX group（29 080.7±2 877.5）（P=0.042）. Conclusion：The number of CNPase+ oligodendrocytes in the CA1 of hippocampus of the CUS rats is significantly decreased. Fluoxetine might prevent the loss of CNPase+ oligodendrocytes in the CA1 of hippocampus of the depression rats induced by CUS. The oligodendrocytes in the CA1 of hippocampus play an important role in the pathogenesis of depression. The current result might provide structural basis for the future studies that search for the new antidepressant strategies.