To evaluate the role of propofol in altering pentylenetetrazol induced seizure threshold in colitis models in rats and its antagonist effect by thalidomide. Total 42 Wister rats of either sex were included in the study. Animals were divided into seven groups (n=6) control group (PTZ, 60mg/kg of b wt ), PTZ low dose group (40 mg/kg of b wt), propofol (5 mg/kg of body weight), propofol (5 mg/kg) + PTZ (40 mg/kg). TNBS induced colitis group (PTZ 40mg/kg b wt), TNBS colitis + propofol (5mg/kg) +PTZ (40mg/kg) and TNBS colitis + propofol (5mg/kg) +PTZ (40mg/kg) and thalidomide 150mg/kg orally for 14 days. The rats were given propofol (5 mg/kg), after 24 hour of I/P injection of propofol rats were subjected to PTZ (40 mg/kg) seizure susceptibility. Following parameters were assessed seizure assesment, morphological score, histological score and biochemical parameters (MPO, MDA, TNF‐α) The results showed onset of seizure was reduced in the propofol groups and TNBS colitis model which was significant different compared to control group (p<0.001). In severity score and duration of seizure was significant elevated in the propofol treated group and TNBS colitis model (p< 0.001). Thalidomide restored lipid peroxide malondialdehyde as well as reduction of myeloperoxidase and TNF‐α towards normal levels. Morphological and histological score were significantly reduced in thalidomide treated groups (p <0.001). Present study showed that propofol reduce the seizure threshold and increase duration of seizure in TNBS induce colitis model. (Supported by PGIMER, Chandigarh, India.)