, the causative agent of cryptococcosis, is the primary fungal pathogen that affects the immunocompromised individuals. Galectin-3 (Gal-3) is an animal lectin involved in both innate and adaptive immune responses. The present study aimed to evaluate the influence of Gal-3 on the infection. We performed histopathological and gene profile analysis of the innate antifungal immunity markers in the lungs, spleen, and brain of the wild-type (WT) and Gal-3 knockout (KO) mice during cryptococcosis. These findings suggest that Gal-3 absence does not cause significant histopathological alterations in the analyzed tissues. The expression profile of the genes related to innate antifungal immunity showed that the presence of cryptococcosis in the WT and Gal-3 KO animals, compared to their respective controls, promoted the upregulation of the pattern recognition receptor (PRR) responsive to mannose/chitin () and a gene involved in inflammation (), as well as the downregulation of the genes related to signal transduction (, , , ) and PRRs (, , ). The absence of Gal-3, in fungal infection, a positively modulated gene involved in phagocytosis () and negatively genes involved in signal transduction ( and ), proinflammatory cytokines and and receptor. Therefore, our results suggest that Gal-3 may play an essential role in the development of antifungal immune responses against cryptococcosis.