TNF-α protein and caspase-3 in mudskipper muscle can be used as a biomarker to evaluate the environmental conditions. Therefore, this study aimed to analyze the heavy metal contents, specifically Cr and Fe, in the sediments from the mangrove area, as well as the expression of TNF-α and caspase-3 in mudskipper muscle. The samples used were the sediments and mudskippers from the waters of Poka, Waai, and Rutong Villages. The heavy metals were analyzed using Atomic Absorption Spectrophotometry (AAS), while the TNF-α and caspase-3 expressions were assessed with immunohistochemical staining. Observations were carried out using an optical microscope with 1000x magnification. The results showed that the proportion of Fe accumulated in mudskipper at the three locations was greater than Cr, while Cr was higher in the sediment compared to Fe. Moreover, the TNF-α and caspase-3 expressions appeared in muscle organs in varying amounts. This indicates that Cr and Fe under excessive conditions can be toxic to mudskipper causing muscle inflammation and cell death, which leads to the expression of TNF-α and caspase-3.