The silkworm, Bombyx mori has great economic and scientific value, as it has long been exploited as a primary silk producer and as a model system for lepidopterans and arthropod studies. This species is highly susceptible to microbial diseases that affect quality and quantity of silk, thereby causing huge economical losses. Insects have developed efficient innate immune system to fight against microbial pathogens. The innate immune system plays a crucial biological role in the limitation of microbial infections by using different immune strategies such as antimicrobial peptides production (AMPs), reactive oxygen species generation and melanin formation. So far, many studies identified different biological factors, which are considered to be involve in the regulation of these biochemical processes in B. mori. Here, we describe, current knowledge on the molecular patterns of various immune factors and also highlight their molecular mechanism of action in the limitation of viral, bacterial and fungal pathogens in B. mori. Furthermore, we discussed different strategies to improve the immune responses of silkworm species. This review will be helpful to understand the molecular aspects of immune factors, and their regulatory mechanism to control microbial diseases in the economically important insect species, B. mori.