Background and aims: Cucurbita maxima Duch (CMD) is used as sedative for tooth and ear pain, but its analgesic effect has not been research in experimental studies. The aim of this study was to investigate the analgesic effect of hydro-alcoholic extract of CMD was studied using formalin model in rats. Methods: In this experimental study, 60 Rats were randomly divided into 6 equal groups. Control group was injected distilled water and three experimental groups were injected CMD extracts (50, 100 and 200 mg/kg). Group 5 received ibuprofen and group 6 received naloxone with the most effective dose of the extract. Extract or drugs were injected 15 minutes before formalin injection. The responses of animals to pain were recorded for 30 min. after the formalin injection. Responses of first 0-5 min. were considered as acute pain and responses of 15-30 min. as chronic pain. Results: CRM extracts reduced acute pain in doses of 100 and 200 mg/kg (P<0.001). In addition, the extract decreased chronic pain in all used concentrations compared to the control group (P<0.001). Naloxone inhibited analgesic effect of the extract (P<0.05). Conclusion: CRM extracts reduce acute and chronic pains in formalin test through opioid system and it might be used as an analgesic drug
