Objective To investigate the effect of the local injection of simvastatin?loaded PLGA microspheres on intervertebral disc degeneration in a rat model. Methods The simvastatin?loaded PLGA microspheres were prepared by a double emulsion method ; at the same time, the characteristics and drug release in vitro of the microspheres were observed. The intervertebral disc degeneration models were injected with simvastatin?loaded PLGA microspheres (experimental group) or saline solution (control group). The rats were sacrificed and evaluated by radiological, histological, and molecular biology analyses at predetermined time points. Results The morphology of the microspheres was homogeneous, with a smooth surface and an average size of about 1. 52 ± 0. 54 μm. Drug loading efficiency and the rate of drug loading of the microspheres were approximately 90. 4 ±2. 6% and 23. 3 ±1. 3%. The drug release rate of the microspheres within the first 24 h was about 45%. In addition, the cumulative release rate was more than 81. 2% in the subsequent 144 h. A single dose of simvastatin?loaded PLGA microspheres injected into the intervertebral disc showed a tendency to increase the mRNA levels of bone morphogenetic protein?2 (BMP?2), collagen type II, proteoglycan, and hypoxia?inducible factor?1α (HIF?1α). The disc height index% (DHI) and MRI scores of the experimental group were all significantly different from those in the control group in the same period. In addition, simvastatin treatment also improved histological changes induced by needle puncture. Conclusions Simvastatin?loaded PLGA microspheres hold great promise for use as a drug?delivery system. The injection of simvastatin?loaded PLGA microspheres into degenerated intervertebral disc may result in the retardation of disc degeneration. Moreover, the expression of collagen type II and proteoglycan was also increased, the mechanism of which might be related to the increased expression of HIF?1α and BMP?2.