Objectives: It is increasingly recognized that modulation of brain inflammation may uncover new potential therapeutic strategies for stroke. Recent studies have shifted focus from immunological implications in ischemic stroke to an even more devastating form; the hemorrhagic stroke. The aim of this study was to investigate the neuroinflammatory response in cerebrospinal fluid (CSF) in patients with primary intracerebral hemorrhage (ICH) associated with intraventricular hemorrhage (IVH) in the presence of the recombinant tissue plasminogen activator (rt-PA). Patients and methods: 88 adults with primary ICH associated with IVH were divided into two groups: group A and group B, which received normal standard of care for this diagnosis. The group B was treated via catheter-based clot lysis using low-dose rt-PA injected through the external ventricular drain (EVD) system, and the group A was treated with saline applied to EVD system in equivalent volume. CSF samples from rt- PA were obtained from the EVD system at four time points: once before the drug administration (day 0), and then 1, 3 and 7. No attempt at randomization was made. The decision to inject rt-PA was based on the preference of the primary attending neurologist and the ability to obtain consent. Temporal interleukin-1 beta (IL-1β), Interleukin 6 (IL- 6) and transforming growth factor beta (TGF-β) concentration changes were analyzed and compared between the two groups. Results: The concentration of IL-1β was significantly lower in the group B than in the group A on day 7. In addition, the concentration of TGF-β was significantly higher in group B than in the group A on day 1. There was a significant difference of IL-1β concentration in group A between day 0 in comparison to day 3 and 7, and same days and time points in both groups where IL-6 concentration was measured. In group B IL- β concentrations on days 1 and 3 were significantly higher than on day 0. We also observed a significant difference in TGF-β concentrations between both groups between day 0 and day 1, 3 and 7. Conclusion: The different pattern of pro- and anti-inflammatory cytokines in patients with ICH associated with IVH suggest distinct characteristics of secondary brain injury depending on the treatment modality.