Background & Objective: Recently, antihistamines is known as analgesic agents. The aim of the present study is to investigate the  analgesic activity of chlorpheniramine (H₁ antagonist), during anesthesia with acepromazine- ketamine combination  and surgical operation in rat.

Methods & materials: 20 adult rats were randomly assigned in two groups. In  first group,  chlorpheniramine was administered  and 30 minutes later acepromazine – Ketamine was  injected.   In second  group, Normal saline was administerd  initially  and  then acepromazine - Ketamine combination was injected.   Assessment of pain reflexes was performed  by toe pinch , tail pinch test and reflex of rats to laparotomy operation during anesthesia. Induction time of anesthesia, duration of light anesthesia, surgical anesthesia time, walking time, heart rate and respiratory rate was measured. 

Results: Time of light anesthesia in group 2    was shorter than group 1 (P < 0.05). Laparotomy pain  score was significantly different in first group and second group. Toe pinch and tail reflex didn’t show significant differences between two groups. Heart rate in all rats not showed significant differences in compared together .  

Conclusion: chlorpheniramine as a premedication was induced  appropriate balance anesthesia in rat with acepromazine- ketamine combination. Thus, chlorpheniramine could be used in rat as premedication agent for surgical operations in combined with acepromazine- ketamine.