Objectives: Possible serotonergic modulation of acute peripheral inflammation was investigated in rat adopting AIR pouch as an experimental model. Methods: AIR pouch type carrageenan-induced inflammation model on the back of the male Wistar rats was used. Injection of carrageenan solution into an AIR pouch induced gradual increases in the pouch fluid volume and leukocytes accumulation in the pouch exudates as well as granulation tissue weight. Granisetron (12.5, 25, 50, 100, 200, 400 & 800mg) was injected at the same time as the carrageenan. Results: Granisetron (50, 100 & 200, 400 mg) was found to inhibit the number of white cells in the exudates at 6 hours after the carrageenan injection significantly (from 119.6 ± 7.8 million in control group to 62.5 ± 6.7 million , 69.5 ± 9.8 million, 82.5 ± 4.8 million and 86.3± 6.3 million respectively). The pouches fluid volumes were decreased significantly by doses of 12.5mg (3.6± 0.1ml), 25mg (3.4 ± 0.1ml), 100mg (3.6 ± 0.2 ml), 400mg (3.7 ± 0.1ml), 800mg (3.6 ± 0.1ml) of granisetron compare to control (4.1 ± 0.08ml). Tissues weight at 6 hr after carrageenan injection was increased by doses of 12.5 mg (5.04 ± 0.6 g) , 25 mg (3.06 ± 0.5 g) and 800 mg (4.7 ± 0.2 g) and was decreased with 100 mg granisetron (1.3 ± 0.2 g) significantly compare to control group (5.04 ± 0.6 g). Conclusion: The study confirms that the serotonergic system is capable of modulating peripheral inflammation via 5HT3 receptors.