Schistosomiasis is a neglected tropical disease. Its treatment relies on the use of a single drug, praziquantel. Due to treatment limitations, an alternative for schistosomiasis chemotherapy is required; thus, a better understanding of parasite biology and host-parasite interactions is valuable to aid the identification of new anti-Schistosoma drugs. The parasite has a complex life cycle, which results in challenges regarding the evaluation of Schistosoma mansoni development and mammalian infection establishment. Accordingly, this protocol describes methodologies to evaluate: (1) adult worm growth; (2) reproduction; and (3) granuloma formation; and consequently allows more comprehensive knowledge of S. mansoni development in a natural biological system.