Please verify the following:
1) Login must be done using an Administrator account. Make sure the user is included in the groups "Administrators", "dotDefenderAdmins" and "IIS_WPG"(IIS6) / "IIS_IUSRS"(IIS7).
2) Check ISAPI filters. (Websites -> properties -> ISAPI Filters)

If an ISAPI filter called URL-Scan is present, it will prevent dotDefenderWS.exe service from running. You must add an exception for dDefender in URL-Scan. (http://learn.iis.net/page.aspx/476/common-urlscan-scenarios/)

Also, avoid .exe filtering. It might block the "dotDefenderWS.exe" file. If you find it in the ISAPI filters, add an exception or remove it completely.

Perform this check on (Websites -> properties -> ISAPI Filters) and also on each website (right-click on each website’s name -> properties ->ISAPI Filters)

In addition, make sure that either an extension (IIS6) or a "dotDefenderModule" (IIS7) exists.
3) The license.dat file may be corrupted.

Open the file, and if you see strange characters instead of clear text, it is corrupted. Replace the license.
4) The dotDefender virtual directory is placed under the Default website.

If the default website is stopped, missing or working in a different port (FTP port 21 for example) the installer will not create a virtual directory.

If a virtual directory isn't found, create it manually under a different site (please contact the Support Team and ask for instructions).

5) Accessing the Default website from within the server sometimes may cause troubles.

Try accessing it from outside (perhaps with a different browser).

6) In case you are NOT using the 'Administrator' account, make sure to disable the UAC

7) Make sure the website and the VD under it are using “DefaultAppPool”, where .NET version there is 2.0.