Background: Leprosy is manifested in varied forms based on the immune status of the patient giving rise to the polar and borderline spectrum of tuberculoid (TT) and lepromatous leprosy (LL). The present study was conducted to assess the macrophage activation in the spectrum of leprosy using CD1a and Factor XIIIa immunohistochemical markers and to correlate the macrophage expression with the morphological spectrum and bacillary index.Methodology: The present study was an observational study.Results: The present study consisted of 40 biopsy-proven leprosy cases, in which a majority were males, and the most common age group was 20-40 years. The most common type encountered was borderline tuberculoid (BT) leprosy. Expression of epidermal dendritic cells and intensity of staining by CD1a was higher in TT (seven of 10 cases (70%)) when compared to LL (one of three cases (33%)). Similarly, Factor XIIIa showed higher expression of dermal dendritic cells in 90% of TT when compared to LL which was seen in 66%.Conclusion: The increased number and strong intensity of dendritic cells in the tuberculoid spectrum may indirectly indicate macrophage activation and possibly account for the low bacillary index.