In this study, the interactions in aqueous binary and ternary systems containing polyethylene glycol (6000) and erythromycin at different temperatures were investigated to utilize this information in the aqueous two-phase method for different purposes, including separation and purification. Through experimental methods, density, sound velocity, and viscosity at 293.15, 303.15, and 313.15 K were measured in aqueous solutions, including erythromycin and polyethylene glycol. From the experimental density data, apparent molar volume (ϕ
V), limiting apparent molar volume (ϕ
V
0) and transfer molar volume (
∆
t
r
ϕ
V
0
)
${{\increment}}_{\mathrm{t}\mathrm{r}}{\phi }_{\mathrm{V}}^{0})$
have been calculated. Also, the experimental sound velocity data determined apparent molar isentropic compressibility (ϕ
k), limiting apparent molar isentropic compressibility (ϕ
k
0) and transfer isentropic compressibility (
∆
tr
ϕ
k
0
)
${{\increment}}_{\mathrm{tr}}{\phi }_{\mathrm{k}}^{0})$
values of polyethylene glycol (6000) from water to erythromycin solutions. Furthermore, experimental viscosity data and the Jones–Dole equation determined viscosity β
′-coefficient and transfer viscosity β
′-coefficient (
∆
t
r
β
′
)
${{\increment}}_{\mathrm{t}\mathrm{r}}{\beta }^{\prime })$
values. The obtained results investigated the polymer effect as kosmotropic or chaotropic on erythromycin drug and the interaction between polyethylene glycol and erythromycin (solute-solute interactions). The results show that the interaction between drug and polymer is more desirable in the high-concentration polymer. Finally, results indicate that polyethylene glycol (6000) has played a kosmotropic role in aqueous solutions of erythromycin.