In situforming gel with solvent exchange mechanism is one of drug delivery systems for periodontitis treatment. The system is injected into the desired site then transforms into a gel state when the solvent diffuses out and aqueous diffuses in. Thein situforming Eudragit RSgels loading 1, 5 and 10%w/w metronidazole (MT) were developed in this study usingN-methyl pyrrolidone (NMP), 2-pyrrolidone and dimethyl sulfoxide (DMSO) as solvent. The viscosity of the gel systems in all solvents were increased as drug or polymer amount was increased with Newtonian flow behavior. Transformation into gel was evident after initiated the systems in phosphate buffer pH 6.8. NMP systems exhibited the lowest work of syringeability through 18 G syringe. Drug release from dialysis tube of DMSO systems was slower than that of NMP and 2-pyrrolidone systems, respectively. Antimicrobial activity againstStaphylococcus aureusof the systems comprising MT using NMP as solvent was greater than that using 2-pyrrolidone and DMSO, respectively, which the antimicrobial activity was increased as the drug amount was increased. Therefore, the solvent type affected the viscosity, gel formation, syringeability, drug release and antimicrobial activity of Eudragit RS systems. These developed systems sustained the drug release and inhibited the bacterial growth hence they were interesting systems for periodontitis treatment.