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Objective(s): Studies indicate that major deficiency in the levels of monoaminergic transmitters is a reason for severe depression. On the other hand, it is shown that Carthamus tinctorius L. (CT) may improve neuropsychological injuries by regulation of the monoamine transporter action. Hence, the present study was undertaken to evaluate the involvement of monoaminergic systems in antidepressant-like effect of CT extract in the tail suspension test (TST) in mice. Materials and Methods: The mice were intraperitoneally (IP) treated with CT extract (100–400 mg/kg) 1hr before the TST. To investigate the involvement of monoaminergic systems in antidepressant-like effect, the mice were treated with receptor antagonists 15 min before CT extract treatment (400 mg/kg, IP) and 1hr before the TST. Results: Findings showed that CT extract (100–400 mg/kg, IP), dose-dependently induced antidepressant-like effect (P