5-Hydroxytryptamine (serotonin) (5-HT) and norepinephrine (NE) are implicated in modulating descending inhibitory pain pathways in the central nervous system. Milnacipran (MLN) is a selective and potent dual 5-HT and NE reuptake inhibitor (SNRI). In the present study, the effects of HMG-CoA reductase inhibitor atorvastatin (ATR) on antidepressant- induced anti-nociception have been investigated. Anti-nociceptive effects were evaluated using formalin test in rats after administration of atorvastatin and milnacipran alone as well as in combination. Fifty microlitre of 2.5% formalin solution was injected subcutaneously into the plantar surface of the right hind paw and nociceptive behavior was observed up to 45 min in the blocks of 5 min. Milnacipran induced a dose-dependent anti-nociception in the first phase as well as in the second phase of the formalin test at the dose levels of 10, 20, 40 and 60 mg/kg, p.o.. Milnacipran significantly attenuated the duration of licking and licking frequency both in second phase. Atorvastatin (1, 5, 10 and 20 mg/kg, p.o.) did not inhibit the nociceptive behavior of formalin significantly when treated alone. A combination of sub-therapeutic doses of the milnacipran (20 and 40 mg/kg, p.o.) with atorvastatin (10 and 20 mg/kg, p.o.) potentiate anti-nociception induced by antidepressant significantly. It is concluded that the atorvastatin modulate the antidepressant-induced anti-nociception in formalin induced inflammatory pain model. However, studies in chronic models of neuropathic pain are required to evaluate the efficacy of milnacipran and atorvastatin combination in rats.