Background The purpose of this study was to evaluate the analgesic effect of Rubus occidentalis extract (ROE) in a rat model of incisional pain. The involved mechanisms and proinflammatory cytokine response were also examined. Materials and methods To investigate the analgesic effect, rats were intraperitoneally administered with normal saline or various doses of ROE before or after a plantar incision. To evaluate the involved mechanism, rats were intraperitoneally administered yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine after a plantar incision; ROE was then administered intraperitoneally. The mechanical withdrawal threshold (MWT) was tested with von Frey filaments at various time points. To determine the inflammatory response, serum levels of interleukin (IL)-1β or IL-6 were measured. Results The MWTs significantly increased at 15 min after postincisional administration of 300 mg/kg ROE when compared with those in the control group. This elevation was observed for up to 45 min. Overall, MWTs increased in proportion to ROE dosage; however, ROEs administered before the incision produced no significant change in the MWT. The analgesic effect of ROE was significantly antagonized by mecamylamine, naloxone, and yohimbine, and agonized by dexmedetomidine. Administration of ROE inhibited the postincisional increase in serum IL-1β and IL-6. Conclusions Intraperitoneal administration of ROE after surgery induces antinociceptive effects in a rat model of postoperative pain, and its effects on mechanical hyperalgesia may be associated with α2-adrenergic, nicotinic cholinergic, and opioid receptors.