Tanshinone IIA (Tan IIA) is the most abundant lipid-soluble component in Salvia miltiorrhiza. Both Tan IIA and its derivatives including Sodium tanshinone IIA sulfonate (STS) have been widely used in clinic due to their proved anti-inflammation, anti-oxidation, and anti-fibrosis functions. Recently, combinations containing Tan IIA and active components have attracted intensive interest in fibrosis. Multiple studies have been conducted to attempt to decipher the mechanisms of this traditional Chinese medicine and found that Tan IIA can attenuate fibrosis through different pathways such as Smad2/3, NF-κB, Nrf2, E2F and snail/twist axis. However, some of the studies were contradictory and confusing. Therefore, it was important to develop an easy-to-access reference for clinic use. In this study, we reviewed the pharmacological mechanisms, pharmacokinetics, and toxicology of Tan IIA and its derivatives in the treatment of fibrosis and introduced the cutting-edge new formulation of Tan IIA compound.