Phytosterols, α-tocopherol and γ-oryzanol are scientifically recognized as major health promoting compounds found in cold-pressed rice bran oil (CRBO). This study aimed at encapsulating CRBO using a niosome delivery system. Water soluble CRBO niosomes approximately 200 nm in size were generated, remained stable for up to four weeks at 4 °C, and exhibited an encapsulation efficacy >80%. CRBO niosome controlled release was possible until the small intestinal phase in in vitro digestion. To our knowledge, this is the first study indicating a globular morphology of the CRBO niosomes and the location of CRBO. M0, M1, and M2 macrophage phenotypes were stimulated with 25, 50, and 100 μg ml-1 of in vitro digested CRBO niosomes. Gene expression profiles for each macrophage cell were obtained via M1 and M2 marker gene analysis. Changes of M0, M1 and M2 macrophage gene expression profiles occurred after CRBO stimulation and were visualized via principal component analysis (PCA). The results revealed a clear M1 macrophage conversion towards M0 in a digested CRBO niosome dose dependent manner, while this was not the case with M0 and M2 macrophages. Our findings indicated that CRBO niosomes have an ability to reverse M1 pro-inflammatory macrophage transformations back to resting M0 macrophages. Moreover, this study also showed future potential uses of CRBO niosomes, containing rice phytosterols and a co-surfactant, as fabricating materials to deliver and to control the release of oil soluble bioactive compounds for water soluble functional ingredient applications.