Selective serotonin reuptake inhibtiors (SSRIs)are a class of compounds typically used as antidepressants in the treatment of depression, antxiety disorders, and some personality disorders, in additon to their antidepressant effects have benn reported to have anti-inflammatory effects. The aim of this study was to assess the anti arthritic potential of two SSRIs, fluoxetine and citalopram, in antigen-induced arthritis (AIA) in mice. This study carried out on thirty six Swiss albino male mice they were eqully divided into six groups , induction of arthritis done on five group, one is postive control and other group treated with flouxitine and citalopram in doses of 25 mg/kg, 10 mg/kg for each, on group kept as negative control. Three parameters of evaluation the induction of arthritis and the healing potency of the SSRIs including clinical score analysis, histological score analysis and cytokine serum analysis. The clinical scoring system shows that fluxitine 25mg / kg / day and 10 mg/kg/day gave a significant result comparing with postive control group (p<0.05), Fluxitine 10 mg/kg /day show healing less than dose of 25 mg/kg, there was still swellowing redness, inflammation during the time of this experiment, Citalopram showed a significant deference value only an a dose of 25 mg/kg (p<0.05). The results in this experiment shown that the decrease in the TNF- alpha level as with histological and clinical score is dose dependent , this also mentioned in another research that found a non significant anti-inflammatory effect of SSRIs if it’s taken in the normal anti depressant dose . (Reis,et al.2009). Fluoxetine and citalopram are normally prescribed for depression at a maximum dosage of 80 mg/day , In this arthritis model ,it needed for suppression of the disease progression much higher doses to decrease the TNF-alpha level . (25 mg/kg, as compared with~ 1 mg/kg used to treat depression in humans).