Objective To evaluate the release characteristics and analgesic effect of extended-release composite polymers of local anesthetics. Methods Polymer extended-release film containing bupivacaine hydrochloride was prepared via electrospinning (nanomembrane, group M), and was furthermore loaded intoPLGA-PEG-PLGA thermo-sensitive gel forming composite extended-release carrier (group G). The in vitro release profile, analgesic effect and safety in vivo were evaluated. Results In vitro, the cumulative release of bupivacaine hydrochloride reached more than 5 d in the group M and 10 d in the group G. In vivo, the analgesic effect in the model of chronic compression injury of sciatic nerve lasted for 14 d in the group M and group G. There was no significant difference between the two groups (P > 0.05). The peak plasma concentration of bupivacaine hydrochloride in the group M was (0.294±0.029)μg/L one day after drug administration, while (0.192±0.064)μg/L in the group G three days after drug administration, which were far below the toxic plasma level of bupivacaine chloride. Meanwhile, there were no significant pathological changes in the heart, liver, spleen, lung and kidney of the two groups. Conclusions In this study, the composite extended-release drug delivery prepared by bupivacaine hydrochloride electrospinning film as the basis and PLGA-PEG-PLGA thermo-sensitive gel can further prolong the release time of bupivacaine chloride and exhibit long-term analgesic effect without toxicity.