Aim: Peripheral nerve blockade is a common regional anesthetic technique in surgical procedures in daily clinical practice. The aim of this experimental study was to compare perineural dexmedetomidine alone with perineural sodium bicarbonate added to dexmedetomidine for measurement of analgesia, sensorial and motor blockade and histopathologic evaluation.Material and Methods: Twenty-four rabbits were randomly allocated to 3 groups; Group S: sham, Group D: perineural dexmedetomidine (20 mcg/kg) and Group D+SB: perineural dexmedetomidine (20 mcg/kg) plus sodium bicarbonate. (8.4%, 0.125 mL). Analgesia measurement was evaluated by hotplate test, the paw withdrawal response was performed for sensorial and motor blockades, also were recorded at baseline, 30, 60, 90 and 120 min after drug administration. Dissected nerve tissue was also examined for histopathologic evaluation.Results: Latency times of Group D or Group D+SB were significantly longer when compared with Group S at 30, 60, 90 and 120 min. There was no significant difference between Group D and Group D+SB for the all scheduled times. Sensorial and motor blockade scores were similar in all groups. Group D or Group D+SB caused edema, inflammation with neutrophil leukocytes, and degeneration of myelin fibers, increased in vacuolization, granulation tissue and fibrosis.Conclusion: Perineural dexmedetomidine alone or in combination with sodium bicarbonate prolonged the duration of analgesia, but did not enhance the sensorial and motor blockade, when compared with placebo. Perineural dexmedetomidine combined with sodium bicarbonate didn’t enhance the blockage. Dexmedetomidine caused edema, inflammation and degeneration of myelin fibers, increased in granulation tissue and fibrosis.