The purpose of this study was to evaluate histopathological inflammation process after RCT in infected teeth of cats following the systemic injection of Penicillin G Procaine. A comparison was made on two groups of with and without drug application. A total of 30 mature, healthy cats were used in this study. One maxillary canine was left intact as control while the othe three canines were used as experimental cases.After intentional overinstrumentation, teeth were exposed to oral cavity for two weeks which then were sealed with glass ionomer and reviewed after 6 weeks. Periapical lesions were clearly seen in radiographs of all teeth. From the total, 9 Cats died and 3 were kept as positive control leaving 18 cats which were put into Three groups. Group I:6 cats were subjected to one visit RCT. Group II: recieved Penicillin G Procaine (IM) 12 hours before RCT. Group III: 6 cats had penicillin G procaine (IM) immediately after RCT. Injections were repeated every 12 hours until the animals were subject to vital perfusion. After RCT, each cat was subjected to vital perfusion at 3,24,48 hour intervals. In positive control cases, periapical lesions were induced followed by vital perfusion without RCT and / or drug application. Canine teeth with periodontium, periapical lesion and some of the normal bone, were separated from the jaw in the form of block section after the sacrification of animals. Decatcification process was performed on each sample. The rate and the type of inflammation and fibroblast prolifration were assessed to find out the differences.Results showed a higher prevalance of chronic inflammation 3 hours after RCT. while this was not the case 24 and 48 hours after RCT. The rate of inflammation and fibroblast prolifration showed no significant difference between the three groups in 3,24,48 hours following RCT.