Rhizopus delemar is the most common cause of mucormycosis, a life threatening invasive fungal infection. The molecular mechanisms that govern the interaction between R. delemar and host cells are poorly understood. Based on previous transcriptional analyses, we hypothesize that the activation of ERK1/2 MAPK signaling pathway and ErbB2 receptor signaling promote fungal invasion of lung epithelial cells. We confirmed that ERK1/2 MAPKs are activated in A549 alveolar epithelial cells upon infection with R. delemar spores or germlings. We also confirmed that the ErbB2 receptor is activated upon infection and hypothesize that the activation of the ErbB2 receptor from the host cell leads to the downstream activation of the ERK1/2. A novel finding was the presence of an ErbB2-like protein encoded by R. delemar that could potentially form dimers with the host encoded ErbB2 or EGFR to activate downstream signaling in the host to promote invasion.