Class Myxosporea includes Myxobolus parasite. Myxosporean species could infect the skeletal muscles of freshwater fish, including Nile tilapia. In this study, four Nile tilapia fish, collected from a fish farm in Dakahleya province, died and showed gross lesions of haemorrhage on the outer surface (external skeletal muscles and fins). Fish was necropsied and samples were collected for both histopathological examination and quantitative analysis of the transcriptional level of interleukin-8 and tumour necrosis factor-α mRNA in selected tissues. Careful examination revealed the residence of myxospore-producing plasmodia in the affected skeletal muscles of Nile tilapia. The morphometric analysis revealed approximate morphometric results to Myxobolus fomenai. The plasmodia were detected in the skeletal muscles, focally replacing the muscle tissue and containing various developmental stages. The parasite was either surrounded with polymorphnuclear and mononuclear cells and few erythrocytes (haemorrhage), together with necrosis of the adjacent myocytes, or it was seen with sparse or without inflammatory reaction. Transcriptional analysis of interleukin-8 and tumour necrosis factor-α in the skeletal muscles, fins, spleen, and head-kidney revealed the slight down-regulation of interleukin-8 and tumour necrosis factor-α mRNA in the skeletal muscles and their slight up-regulation in the fins of infected fish. However, their mRNA levels in the spleen and head-kidney remained unaffected by infection. Careful future histopathological examination is required to reveal the possibility of Myxobolus fomenai infection in other organs of Nile tilapia. In addition, further immunological investigation needs to be accomplished in relation to such parasitological infestation.