Inclusion type and concentration in steel is critical in steelmaking, affecting both productivity through clogging, and downstream physical properties of the steel. They are normally removed from steel by reacting with a slag phase. For efficient inclusion removal the inclusions must attach/bond with the slag phase. The strength of the attachment can be characterized by the wettability of the slag on the inclusions. In this study, the interface characteristics between solid spinel (MgAl2O4) with low porosity of 1.9% and ladle slags of the CaO-Al2O3-SiO2-MgO were investigated, in particular the contact angle was measured at 1500 °C using a modified sessile drop technique for different CaO/Al2O3 mass percent ratios ranging from 0.98 to 1.55. Characteristic curves of wettability (θ) versus time showed a rapid decrease in wetting in the first 10s tending to a plateau value at extended times. The chemical interaction at the interface between spinel (MgAl2O4) and slag was analyzed by carrying out detailed thermodynamic evaluation and characterization using scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS). There is evidence of the slag penetrating the substrate via pores and along grain boundaries, forming a penetration layer on the substrate. The depth of the penetration layer was found to be a function of cooling rate. It decreased from ~190μm to ~50μm for a slow cooled slag-spinel substrate sample in the furnace to a rapidly cooled slag-spinel substrate sample respectively.