Paccal Vet (Osamia Pharmaceuticals) is a water‐soluble nanoparticle micellar formulation of the drug paclitaxel that is well tolerated in dogs. This study evaluated the in vitro effect of Paccal Vet on two canine hemangiosarcoma (HSA) cell lines and their expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Paccal Vet caused HSA cell death in a dose‐ and time‐dependent manner. The 50% inhibitory concentration (IC50) for the two HSA cell lines were 7 to 610 ng/mL, which are clinically achievable. Cell cycle analysis through flow cytometry showed cell cycle arrest at G2/M phase. Annexin‐V and caspase 3/7 activity assays showed significant increases in apoptosis in correlation with the IC50 in each cell line. Reverse transcriptase‐PCR was performed on the cell lines to validate the gene expression of VEGF and bFGF. Results obtained from this study support future studies involving the use of paclitaxel (micellar) for treatment of canine HSA.