Lipolysis triggered adipose tissue remodeling (AT) in periparturient cows is characterized in part by macrophage infiltration and aggregation. In cows with metabolic diseases, characterized by intense and protracted lipolysis, macrophage accumulation in AT is exacerbated and may promote tissue dysfunction. In rodent models, lipolysis triggers macrophage recruitment coupled with increased expression of SPP1, the gene that encodes osteopontin. This chemotactic cytokine recruits cells expressing CD44 glycoprotein that include preadipocytes and macrophages. Our study evaluated the transcription of SPP1, CD44, and additional gene networks related to macrophage infiltration and AT remodeling using qPCR. Subcutaneous AT samples were collected from multiparous dairy cows (n = 22) at 10 d prepartum (dry), 10 d (fresh), and 24 d (lactation) postpartum. Data were analyzed in R using lognormal distributions and pairwise comparisons. SPP1 expression was higher in fresh compared with dry (P < 0.05). A positive relationship in SPP1 expression with large adipocytes (P < 0.05) suggested that cows with greater adiposity, those that are more prone to disease, recruit more macrophages. There was an increase in CD44 gene expression in lactation when compared with fresh (P < 0.01). This finding indicates that CD44, a receptor of SPP1, increases when lipolysis and SPP1 are higher. Expression of SIRPA, a mononuclear immune cell marker, was higher in dry compared with fresh and lactation (P < 0.01). Reduction of SIRPA in fresh and lactation indicates an increase in macrophage phagocytic activity. IL10 had a positive relationship with adipocyte volume in both fresh and lactation (P < 0.05). In human models, IL10 is responsible for the induction of osteopontin in a time- and dose-dependent manner. Upregulation of SPP1 alongside increases in IL10 indicate an association between osteopontin and AT macrophage recruitment in periparturient cows. Future studies will evaluate the potential of osteopontin as a biomarker for macrophage infiltration into AT.