Pharmacokinetics of tolfenamic acid as a single drug (4 mg/kg, intramuscularly) and its co-administration with moxifloxacin (5 mg/kg, intramuscularly) in wistar rats were studied. The plasma drug concentration of tolfenamic acid was assayed by LC-MS/MS. Following intramuscular administration of tolfenamic acid as single drug and in combination with moxifloxacin in male rats, the mean values of observed peak plasma drug concentration (Cmax), area under plasma drug concentration-time curve (AUC(0-¥) ), volume of distribution (Vz), half-life (t½) and clearance (Cl) were 4111.44 ± 493.15 and 3837.69 ± 351.83 ng/ml, 20280.77 ± 3501.67 and 15229.18 ± 678.80 ng.h/ml, 822.17 ± 115.38 and 1249.64 ± 139.52 ml, 2.59 ± 0.16 and 3.27 ± 0.32 hr, and 218.39 ± 25.47 and 265.18 ± 11.36 ml/hr, respectively. The peak plasma drug concentration (Cmax) was significantly higher in female rats compared to male rats. The volume of distribution (Vz) of the drug was significantly higher (P < 0.05) in moxifloxacin-treated male rats compared to female rats. Concomitant administration of moxifloxacin may alter the disposition of tolfenamic acid in male rats.