The degradation behavior of poly(lactic-co-glycolic acid) (PLGA) is important for its application as a biomaterial. In this work, the influence of nano-hydroxyapatite (nano-HA) on the degradation behavior of PLGA matrix was studied. PLGA-based in situ forming system containing nano-HA was prepared using the immersion precipitation method and the polymer hydrolysis was investigated in a phosphate buffer (pH 7.4) at 37 degrees C. The pH values in the testing medium were evaluated to quantify the degradation process. Gel permeation chromatography and scanning electron microscopy techniques were employed to monitor changing of the weight-average molecular weight (M-W) and the body structures of PLGA matrices, respectively. To model the M-W changes, a first-order degradation model was employed. The formed PLGA matrices had different porosities that effected water penetration into the matrices following the hydrolysis process. The obtained degradation rate constant using a mathematical model for PLGA matrices with different nano-HA content was about from 2.5 to 4.5 times lower than neat PLGA matrix. POLYM. ENG. SCI., 59:1028-1035, 2019. (c) 2019 Society of Plastics Engineers