Sickness behavior is a behavioral changes occurring soon after the onset of infection, trauma, and inflammatory processes. In animals, systemic administration of lipopolysaccharide (LPS) induces a characteristic set of responses that has been termed "sickness behavior". Recent empirical results have provided an evidence that inhibition of the production of nitric oxide (NO) from L-arginine (L-Arg) by N^G-nitro-L-arginine methyl ester (L-NAME) accentuated LPS-induced sickness behaviors in male rats. The impact of the L-Arg on LPS-induced sickness behaviors in rats has not yet been tested. To evaluate the possible participation of L-Arg/NO pathway in LPS-induced sickness behaviors, rats were tested in the open field test using LE8811 Actimeter PanLAB device. Rats were weighed, randomly divided into 4 groups (five rats in each group), and intraperitoneally injected as follow: Control group (saline, 0.1ml/100g b.wt), LPS group (LPS, 1 mg/kg b.wt), L-arginine group (L-Arg, 10 mg/kg b.wt, for 7 days), and LPS+L-arginine group (L-Arg, 10 mg/kg b.wt, for 7 days then once injected with LPS, 1mg/kg). Locomotor and behavioral activity levels of the animals were evaluated to measure horizontal activity (units), vertical activity (units), stereotype (units) movements, total distance traveled (cm), and average velocity. LPS decreased locomotor and behavioral activities but not reaching significance. In contrast, the pretreatment with L-Arg was associated with an increase in locomotor and behavioral activities but also not reaching significance. Interestingly, pretreatment with L-Arg of LPS-treated rats accentuated locomotor and behavioral changes induced by LPS. In conclusion, the results of this study support the hypothesized relationship between NO synthesis and modulation of sickness behaviors and suggest that NO may has a dual role in the modulation of sickness behaviors depending on intensity and stage of inflammation.