AIM- The aim of the present investigation is to evaluate the effect of oxidative stress parameters in forced swimming model. MATERIAL & METHODS- Forced swim test is commonly used pharmacological model to study antidepressant activity (Porsolt et al., 1997). The apparatus consisted of transparent cylinder (50cmhigh x20cmwide) and water at room temperature was filled to 30 cm depth. For preparation of homogenate, the fresh whole brain was weighed and transferred to a glass homogenizer and homogenized in an ice bath after adding 10 volumes of 0.9% sodium chloride solution. The homogenate was centrifuged at 3000 rpm for 10 minutes and the resultant cloudy supernatant liquid was used for estimation of cholinesterase and In vivo antioxidant level. RESULTS- The cut off value of 200 and 1/5th dose double of 400 mg/kg were selected for activity. Ethanolic extract significantly (p < 0.01) shortened the immobility time in dose dependent manner in comparison to the control values. However, impiramine treated groups showed significant reduction (p < 0.01) in immobility time as compared to the control. Ethanolic extract of Nyctanthes arbor-tristis at dose of 200 mg/kg and 400 mg/kg p.o significantly (p<0.01) reduced the levels of cholinesterase as compared to scopolamine treated groups by Ellman’s kinetic calorimetric method, which is considered as indicator of inhibition of cholinesterase activity in rat brain after 14 days of treatment. Imipramine treatment also significantly (p<0.01), increased the catalase level compared to the corresponding diseased groups respectively. CONCLUSION- This study may also provide more evidence that Nyctanthes arbor-tristis extract, as an antioxidant medication, can be a novel type of antidepressant with memory enhancing properties.