Baicalein (BA) is a flavonoid extract from the root of Scutellaria baicalensis Georgi with excellent biological activities, such as antioxidant and anti-inflammatory activities. However, its poor water solubility limits its further development. This study aims to prepare BA-loaded Solutol HS15 (HS15-BA) micelles, evaluate the bioavailability, and explore protective effects on carbon tetrachloride (CCl4) induced acute liver injury. The thin-film dispersion method was used to prepare HS15-BA micelles. The physicochemical, in vitro release, pharmacokinetics, and hepatoprotective effects of HS15-BA micelles were studied. The optimal formulation showed a spherical shape by characterization of the transmission electron microscope (TEM) with an average small size (12.50 nm). The pharmacokinetic results illustrated that HS15-BA increased the oral bioavailability of BA. The in vivo results showed that HS15-BA micelles significantly inhibited the activity of the CCl4-induced liver injury marker enzymes aspartate transaminase (AST) and alanine transaminase (ALT). Also, CCl4 induced oxidative damage to liver tissue, leading to increased L-glutathione (GSH) and superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) activity, while HS15-BA significantly reversed the above changes. Moreover, BA also had a hepatoprotective effect through anti-inflammatory activity; the results of ELISA and RT-PCR revealed that HS15-BA pretreatment significantly inhibited the increase in the expression of inflammatory factors induced by CCl4. In summary, our study confirmed that HS15-BA micelles enhanced the bioavailability of BA, and showed hepatoprotective effects through antioxidant and anti-inflammatory activities. HS15 could be considered a promising oral delivery carrier in treating liver disease.