The molecular mechanism underlying muscular atrophy and gravisensing during spaceflight is still unknown. The major effects of spaceflight on body-wall muscles of Caenorhabditis elegans (C. elegans) in the structures and functions were examined, and five important muscle-related genes and three proteins were studied after nearly 15-day spaceflight. The changes for the wall-muscles were observed in situ. Decreased muscle fiber size was observed with myosin immunofluorescence and duller dense-body staining in flight samples, which suggested that muscular atrophy had happened during spaceflight. However, F-actin staining showed no differences between the spaceflight group and ground control group. Otherwise, after returning to the earth the C. elegans displayed reduced rate of movement with a lower ratio (height/width) in crawl trace wave, which indicated a functional defect. These results demonstrated that C. elegans muscular development was changed in response to microgravity, and changes also occurred at the level of gene transcription and protein translation. Expression of dys-1 increased significantly in body-wall muscles, while hlh-1, myo-3, unc-54 and egl-19 RNA levels decreased after spaceflight. Dystrophin (encoded by dys-1) is one of important components in dystrophin-glycoprotein complex (DGC). Increased dys-1 expression after flight implied that the muscular cell would accept more gravity signals by DGC in microgravity in order to keep mechanical balance within the cells. It is concluded that DGC was involved into the mechanical transduction in body-wall muscles of C. elegans when gravity varied, which potentially played a vital role in gravisensing. The changes of hlh-1, myo-3, unc-54 and egl-19 suggested that they had the effects of promoting microgravity-induced muscular atrophy in structure and function aspects. Result of Western blotting showed that the level of myosin A in spaceflight group decreased, further confirmed that atrophy happened during flight.