Continuous exposure to ultraviolet B (UVB) light can increase the amount of melanin, causing hyperpigmentation on the skin. This process involves the important role of Tumor Necrosis Factor-α (TNF-α) and Superoxide Dismutase (SOD). Artocarpus Altilis contain flavonoids that have anti-inflammatory potential, can reduce TNF-α levels and increase SOD which affects the melanogenesis process. To determine the effect of administering Artocarpus Altilis extract serum on TNF-α and SOD levels in guinea pigs exposed to UVB. This research is an in vivo experimental study with Post Test Only Group design, which was conducted at the IBL FK Laboratory (Integrated Biomedical Laboratory Faculty of Medicine) Unissula. A total of 30 male guinea pigs were divided into 5 groups, namely: Group 1 sham, group 2 negative control, group 3 treated with 2% Artocarpus Altilis extract serum, group 4 treated with 4% serum and group 5 treated with 6% serum. Then analyzed using the One-way ANOVA test to determine differences between groups. The lowest mean TNF-α levels were found in group P2 (4.958), other values were P1 (5.820), P3 (5.964), KS (6.069) and KN (5.811). Meanwhile, the average SOD levels in all groups were not much different, P2 (5.802), P1 (5.975), P3 (5.906), KS (6.054) and KN (6.000). In the One-way ANOVA test on TNF-α and SOD there was no significant difference, p>0.05. Administration Artocarpus Altilis extract serum, especially 4%, caused a decrease in TNF-α levels but was not significant, and there was no increase in SOD levels, in guinea pigs exposed to UVB light.