Background: Local anesthetics act by different mechanisms to produce their effects in control acute and chronic pain. Methods: A total of 22 patients (14 female, 8 male) who need tooth apisectomy under infiltration local anesthesia were examined in two situations: Before and after administration of local anesthesia. For all patients salivary sample has been collected by salivette to estimate the level of opiorphin using ELISA Kits, the pain was assessed after administration of local anesthesia using Visual Analogue Scale (VAS). Results: the results showed a significant differences of salivary opiorphin before and after administration of local anesthesia (5.96+5.38) ng/ml and (14.49±3.66) ng/ml respectively with p<0.05, the results also showed that the pain assessment by VAS was (0.831±0.4587) with inverse correlation between the VAS and salivary opiorphin levels but with no significant difference (p>0.05). Conclusions: local anesthetics (xylocaine 2%+adrenalin 1:80,000) used in apisectomy by infiltration technique produce a significant effects on salivary opiorphin (p<0.05) which may suggest a possible effects of local anesthetic on enkephalin pathway and the possibility of using this parameter for measurements of local anesthetic effects.