The purpose of this study was to develop novel lidocaine microspheres. Microspheres were prepared by the oil-in-water (o/w) emulsion technique using poly(d,l-lactide-co-glycolide acid) (PLGA) for the controlled delivery of lidocaine. The average diameter of lidocaine PLGA microspheres was 2.34 +/- 0.3 m. The poly disperse index was 0.21 +/- 0.03, and the zeta potential was +0.34 +/- 0.02 mV. The encapsulation efficiency and drug loading of the prepared microspheres were 90.5% +/- 4.3% and 11.2% +/- 1.4%. In vitro release indicated that the lidocaine microspheres had a well-sustained release efficacy, and in vivo studies showed that the area under the curve of lidocaine in microspheres was 2.02-2.06-fold that of lidocaine injection (p < 0.05). The pharmacodynamics results showed that lidocaine microspheres showed a significant release effect in rats, that the process to achieve efficacy was calm and lasting and that the analgesic effect had a significant dose-dependency.