The objective of endodontic treatments is to control infection and avoid the reinfection of the root canal system. intracanal medication has been used as a subordinate therapy in endodontic treatments after preparing the root canal system. Dentistry requires contact with variable restorative and auxiliary dental materials with different composition; these materials may cause leakage and release substances which have allergenic reaction when interact with the tissues causing hypersensitivity effect producing changes in both the surrounding materials and tissues Aim of the study To analyze tissue responses of Wistar rats to calcium hydroxide (calcipast) , calcium hydroxide iodoform (calcipaste fort) and 2% chlorhexidine gel intracanal medicaments at different implantation time intervals. Methods: 90 specimens were randomly implanted subcutaneously of rats dorsal surface with a polyethylene tubes containing the following substances: calcium hydroxide (calcipast), 2% chlorhexidine gel and calcium hydroxide iodoform (calcipaste fort) intracanal medicaments (test groups). However subcuateneous implantations of 30 specimens of empty polyethylene tubes (control group) were performed; Rats were distributed according to time intervals of evaluation at 1, 2 and 4 weeks. The histological sections were stained with Harris hematoxylin and eosin then evaluations were made in a digital Microscope at X40, X100, and X400 magnifications for quantitative evaluations of inflammatory cells. Results: It was observed that between the tested materials, calcipast fort (group 4) showed the least inflammatory rats tissue reaction, followed by chlorohexidine (group 3) then calcipast group (group 2) at all tested time intervals in comparison to control group (group1). Conclusion: Calcipast fort showed good biocompatibility when compared with chlorohexidine and calcipast intracanal medications.