Yogurt is a food probiotic which are enriched with microbes that can raise the body's immune system. Rosella (Hibiscus sabdariffa Linn.) is known to have anthocyanin compounds that have antioxidant and immunomodulatory effects. The aim of this research was to determine the effect of immunomodulatory activity of yogurt which fortified by rosella (Hibiscus sabdariffa L.) extract to increase the secretion of Reactive Oxygen Intermediate (ROI) and Nitric Oxide (NO). This research was conducted in vivo using 25 male mices with Balb/C strain divided into 5 groups consisted of normal group, plain yogurt treated group and plain yogurt added with 2%, 4%, and 8% rosella yogurt treated group. Treatment was given for 21 days orally. On the 22nd day, the mice were sacrificed, the peritoneum macrophage cells were taken and then tested for the level of Reactive Oxygen Intermediate (ROI) and Nitrite Oxide (NO). The results showed that there was an increase of ROI and NO secretion in 2%, 4%, and 8% rosella yogurt treated groups compared to plain yogurt group. The fortification of yogurt with rosella extract and honey increased the potency of yogurt in increasing the immunomodulatory activity.