Objectives: The understanding of the molecular events of inflammation in the pulp complex is substantial to facilitate the repair and regeneration occurring in caries teeth. This study aims to assess the protease-activated receptor-2 and alpha-smooth muscle actin (α-SMA) in the pulp tissue of caries teeth and their relations with the caries depth and the presence of pulp tissue exposure. Method: This is a cross-sectional study of 150 extracted teeth with their pulp tissue (108 with caries and 42 without caries, considered as a control group). Samples were collected in Duhok/Iraq from April 2016 to August 2017. The immunohistochemical results for both markers were analyzed. Results: Among the dental caries group, 23.15% (n=25) were shallow caries and 76.85% (n=83) were deep caries. Both markers were significantly higher in caries teeth, but the high percentage was negative for the protease-activated receptor-2 in deep caries (47.2%) and even higher in exposed pulp tissue (51.8%), whereas the α-SMA showed greater positivity in deep caries (59.3) and in exposed pulp tissue (45.8). Conclusion: Detecting high results for both markers in caries teeth, with lower protease-activated receptor 2 results in deep caries, needs more studies, as it may reflect the improper use of anti-inflammatory drugs in our society. The high positive for alpha-smooth muscle actin in deep caries may support this conclusion since it is not affected by this treatment. Keywords: Protease-activated receptor-2, Alpha-smooth muscle actin, Pulp tissue, Dental caries