Bacterial surface layers (S-layers) are cell envelope structures ubiquitously found in gram-negative and gram-positive bacteria, including Lactobacillus. S-layers play a role in the determination and maintenance of cell shape as virulence factors, mediate cell adhesion, and regulate immature dendritic and T cells. In this study, we sought to understand the involvement of MAPK serine/threonine kinases in alterations in Endometrial epithelial cells (ESC) growth induced by Lactobacillus crispatus (L. crispatus) slpA, an S-layer protein. We applied various concentrations of L. crispatus to cultured ESCs and observed growth and changes in the phosphorylation status of ERK1/2, JNK, and p38. Similar experiments were conducted using L. crispatus lacking and overexpressing slpA. We found that ESC growth was altered by slpA primarily via ERK1/2. Our findings suggest that L. crispatus slpA promotes ESC growth mainly through an ERK1/2-dependent pathway.