In situ forming drug delivery system is prepared by phase inversion technique using poly (D,L-lactic-co-glycolide) and leuprolide acetate dissolved in N-methyl-2-pyrrolidone. The effects of ethyl heptanoate and glycerol additives are important determinant as rate modifying agents on the drug release kinetics in biodegradable in situ forming porous systems of poly(D,L-lactide-co-glycolide) (PLGA) in N-methyl-2-pyrrolidone (NMP). The release performance and porous structure morphology are investigated by scanning electron microscopy and UV-visible spectroscopy techniques to study the effect of additives. The experimental results exhibit the crucial role of ethyl heptanoate and glycerol at different loadings (1, 3, and 5% w/w) on release profile of leuprolide acetate loaded on poly(D,L-lactide-co-glycolide)hydroxylated (PLGA-H). Both additives at different concentrations reduce the burst effect, while increasing duration of drug release. Ethyl heptanoate, however, shows stronger effect than glycerol. The results of morphological studies show that ethyl heptanoate reduces the porosity of the polymer surface and interconnected tear-like structures of the bulk disappear while the sponge-like structures are observed. In this system glycerol reduces the surface porosity intensively, while the interconnected tears change into channel-like structures. Therefore, morphological results confirm the effect of additives on leuprolide release profile. (C) 2007 Wiley Periodicals, Inc.