Periapical lesions are one of the common pathological conditions affecting periradicular tissues. The microbial invasion and subsequent infection of the canal systems of root play a decisive role in the initiation and progression of periapical lesions. A well-planned and executed access, biomechanical preparation of root canal system followed by three-dimensional obturation contributes to successful treatment outcomes. Hence; in the present report, we described the case of non-surgical healing of a peri-apical lesion with Calcium Hydroxide Powder Mixed with 2% Chlorhexidine Solution. Mixture of Calcium hydroxide with chlorhexidine has a great value in Endodontics, being indicated for several clinical conditions. It has proved to be an effective intracanal medicament and resulted in successful resolution of the peri-apical lesions. Key words: Peri-apical lesion, Calcium hydroxide